2021 Fiscal Year Final Research Report
Properties of steroidogenesis, M1/M2 polarization, and adhesion to niche-forming cells in tissue-resident macrophages
| Project/Area Number |
19K06406
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 42020:Veterinary medical science-related
|
|---|
| Research Institution | Osaka Prefecture University |
|---|
Principal Investigator |
Ogawa Kazushige 大阪府立大学, 生命環境科学研究科, 教授 (60231221)
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | 組織在住マクロファージ / 精巣間質マクロファージ / 肺間質マクロファージ / クッパー細胞 / ニッチ / プロゲステロン / Eph / ephrin |
|---|
| Outline of Final Research Achievements |
Testicular interstitial macrophages, lung interstitial macrophages, and liver tissue-resident macrophages were successfully propagated by mixed culturing with the respective organ-specific stromal cells. It was newly found that (i) testicular interstitial macrophages expressed the androgen receptor and produced progesterone whose production was significantly upregulated by cAMP and a β adrenergic agonist, and downregulated by M1 polarization inducers; (ii) lung interstitial macrophages treated with the M1 polarization inducers induced to express iNOS (a typical marker of the M1 phenotype) and stably expressed arginase 1 (a typical marker of the M2 phenotype), which was constantly expressed at the steady-state, although recruited macrophages do not highly express both molecules at the same time; (iii) EphA/ephrin-A and EphB/ephrin-B molecular system induced to promote the adhesion of liver tissue-resident macrophages to the mimic surface of sinusoidal endothelial cells.
|
| Free Research Field |
細胞生物学
|
| Academic Significance and Societal Importance of the Research Achievements |
精巣間質マクロファージ（Mφ）のプロゲステロン（P4）産生は世界初の知見である。ライディッヒ細胞のテストステロン産生・分泌において精巣間質MφのP4を介した局所的な制御機構の存在が示唆されるため，精巣間質MφのP4産生制御は不妊治療のシーズになる。肺間質Mφは分化途中の肺胞Mφと考えられてきたため，研究は進んでいない。開発した方法では大量の肺間質Mφが得られるため，今後の研究への活用が期待できる。肝常在Mφの定着機構は不明であったが，EphA/ephrin-A，EphB/ephrin-Bシグナルを介する肝常在Mφ接着増強を見出した研究結果から，定着機構の一端が解明されたと考えられる。
|
